Central position of the human histo (blood) group O(H) and phenotype-determining enzymes in growth and infectious disease
The human ABO(H) blood group phenotypes arise from the evolutionarily oldest genetic system found in primate populations, but they originated in critical molecular complementarity with distinct eukaryotic and prokaryotic pathogens, while the development of non-O(H) phenotypes is associated with impaired formation of adaptive and innate immunoglobulin specificities due to clonal selection and phenotype formation in plasma proteins. Indeed, compared with individuals with blood group O(H), blood
... group O(H), blood group A individuals not only have a significantly higher risk of developing certain types of cancer but also exhibit high susceptibility to malaria tropica or infection by Plasmodium falciparum. Thus, the phenotype-determining blood group A glycotransferase(s), affecting the levels of anti-A/Tn cross-reactive immunoglobulins in phenotypic glycosidic accommodation, might also mediate adhesion and entry of the parasite to host cells via trans-species O-GalNAc glycosylation of abundantly expressed serine residues, arising throughout the parasite's life cycle, while excluding the possibility of antibody formation against the resulting hybrid antigen. In contrast, human blood group O(H), lacking this enzyme and providing the molecular mechanism of protecting human reproduction, is indicated to confer a survival advantage regarding the overall risk of developing cancer, and individuals with this blood group rarely develop life-threatening infections involving evolutionarily selective malaria strains.